Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elu...Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elucidated based on extensive spectroscopic data analyses,13 C NMR chemical shifts calculations coupled with the DP4+probability method,and the calculated and experimental electronic circular dichroism(ECD)spectra.Compounds 1–3 showed significant inhibitory activity against pancreatic lipase(PL).The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.展开更多
Psoraleae Fructus(the dried fruits of Psoralea corylifolia), one of the most frequently used Chinese herbs in Asian countries, has a variety of biological activities. In clinical settings, Psoraleae Fructus or Psorale...Psoraleae Fructus(the dried fruits of Psoralea corylifolia), one of the most frequently used Chinese herbs in Asian countries, has a variety of biological activities. In clinical settings, Psoraleae Fructus or Psoraleae Fructus-related herbal medicines frequently have been used in combination with a number of therapeutic drugs for the treatment of various human diseases, such as leukoderma, rheumatism and dysentery. The use of Psoraleae Fructus in combination with drugs has aroused concern of the potential risks of herb-drug interactions(HDI) or herb-endobiotic interactions(HEI). This article reviews the interactions between human drug-metabolizing enzymes and the constituents of Psoraleae Fructus;the major constituents in Psoraleae Fructus, along with their chemical structures and metabolic pathways are summarized, and the inhibitory and inductive effects of the constituents in Psoraleae Fructus on human drug-metabolizing enzymes(DMEs), including target enzyme(s), its modulatory potency, and mechanisms of action are presented. Collectively, this review summarizes current knowledge of the interactions between the Chinese herb Psoraleae Fructus and therapeutic drugs in an effort to facilitate its rational use in clinical settings, and especially to avoid the potential risks of HDI or HEI through human DMEs.展开更多
Qing-Fei-Pai-Du decoction(QFPDD)is a Chinese medicine compound formula recommended for combating corona virus disease 2019(COVID-19)by National Health Commission of the People's Republic of China.The latest clinic...Qing-Fei-Pai-Du decoction(QFPDD)is a Chinese medicine compound formula recommended for combating corona virus disease 2019(COVID-19)by National Health Commission of the People's Republic of China.The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery,viral shedding,hospital stay,and course of the disease.However,the effective constituents of QFPDD remain unclear.In this study,an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD.A total of 405 chemicals,including 40 kinds of alkaloids,162 kinds of flavonoids,44 kinds of organic acids,71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature.With the help of the standards and in vitro metabolites,195 chemical components(including 104 prototypes and 91 metabolites)were identified in mice serum after oral administration of QFPDD.In addition,165,177,112,120,44,53 constituents were identified in the lung,liver,heart,kidney,brain,and spleen of QFPDD-treated mice,respectively.These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.展开更多
Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibi...Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae(FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL(IC50 < 10 μmol·L-1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate(4-MUO) hydrolysis, with the Ki values of 1.61, 3.77 and 10.16μmol·L-1, respectively. Furthermore, docking simulations indicated that two chalcones(isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.展开更多
Herbal medicines play a crucial role in the healthcare system in China and other East Asian countries,and also have been used as alternative medicines in most Western countries[1-3].However,in most cases,the metabolic...Herbal medicines play a crucial role in the healthcare system in China and other East Asian countries,and also have been used as alternative medicines in most Western countries[1-3].However,in most cases,the metabolic fates of herbal constituents and their effects on drug metabolism or endogenous metabolism in the human body have not been well-investigated[4-5].Notably,the concomitant use of herbal medicines may lead to clinically relevant herb-drug interactions or adverse reactions or even metabolic disorders,when some herbs are co-administrated with those drugs with narrow therapeutic indices(e.g.warfarin,digoxin,thyroid hormones and some anticancer agents)[6-8].展开更多
Cephalotaxus is the only genus of Cephalotaxaceae family,and its natural resources are declining due to habitat fragmentation,excessive exploitation and destruction.In many areas of China,folk herbal doctors tradition...Cephalotaxus is the only genus of Cephalotaxaceae family,and its natural resources are declining due to habitat fragmentation,excessive exploitation and destruction.In many areas of China,folk herbal doctors traditionally use Cephalotaxus plants to treat innominate swollen poison,many of which are cancer.Not only among Han people,but also among minority ethnic groups,Cephalotaxus is used to treat various diseases,e.g.,cough,internal bleeding and cancer in Miao medicine,bruises,rheumatism and pain in Yao medicine,and ascariasis,hookworm disease,scrofula in She medicine,etc.Medicinal values of some Cephalotaxus species and compounds are acknowledged officially.However,there is a lack of comprehensive review summarizing the ethnomedicinal knowledge o f Cephalotaxus,relevant medicinal phytometabolites and their bioactivities.The research progresses in ethnopharmacology,chemodiversity,and bioactivities of Cephalotaxus medicinal plants are reviewed and commented here.Knowledge gaps are pinpointed and future research directions are suggested.Classic medicinal books,folk medicine books,herbal manuals and ethnomedicinal publications were reviewed for the genus Cephalotaxus(Sanjianshan in Chinese).The relevant data about ethnobotany,phytochemistry,and pharmacology were collected as comprehensively as possible from online databases including Scopus,NCBI PubMed,Bing Scholar,and China National Knowledge Infrastructure(CNKI).44 Cephalotaxus"',and the respective species name were used as keywords in database search.The obtained articles of the past six decades were collated and analyzed.Four Cephalotaxus species are listed in the official medicinal book in China.They are used as ethnomedicines by many ethnic groups such as Miao,Yao,Dong,She and Han.Inspirations are obtained from traditional applications,and Cephalotaxus phytometabolites are developed into anticancer reagents.Cephalotaxine-type alkaloids,homoerythrina-type alkaloids and homoharringtonine(HHT)are abundant in Cephalotaxus,e.g.,C.lanceolata,C.fortunei var.alpina,C.griffithii,and C.hainanensis,etc.New methods of alkaloid analysis and purification are continuously developed and applied.Diterpenoids,sesquiterpenoids,flavonoids,lignans,phenolics,and other components are also identified and isolated in various Cephalotaxus species.Alkaloids such as HHT,terpenoids and other compounds have anticancer activities against multiple types of human cancer.Cephalotaxus extracts and compounds showed anti-inflammatory and antioxidant activities,immunomodulatory activity,antimicrobial activity and nematotoxicity,antihyperglycemic effect,and bone effect,etc.Drug metabolism and pharmacokinetic studies o f Cephalotaxus are increasing.We should continue to collect and sort out folk medicinal knowledge of Cephalotaxus and associated organisms,so as to obtain new enlightenment to translate traditional tips into great therapeutic drugs.Transcriptomics,genomics,metabolomics and proteomics studies can contribute massive information for bioactivity and phytochemistry of Cephalotaxus medicinal plants.We should continue to strengthen the application of state-of-the-art technologies in more Cephalotaxus species and for more useful compounds and pharmacological activities.展开更多
Huosu Yangwei(HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the...Huosu Yangwei(HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD,AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81803397 and 81522050)the Science and Technology program of Qinghai Province(No.2018-ZJ-739)+1 种基金the Drug Innovation Major Project(Nos.2018ZX09711001-001-001,2018ZX09711001-001-003,and 2018ZX09711001-001-008)the Special Research Fund for Central Universities,Peking Union Medical College(No.3332018088)
文摘Purpurolides D–F(1–3),three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system,were isolated from the endophytic fungus Penicillium purpurogenum IMM 003.Their structures were unambiguously elucidated based on extensive spectroscopic data analyses,13 C NMR chemical shifts calculations coupled with the DP4+probability method,and the calculated and experimental electronic circular dichroism(ECD)spectra.Compounds 1–3 showed significant inhibitory activity against pancreatic lipase(PL).The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.
基金supported by the NSF of China(Nos.81922070,81973286,81773687)the National Key Research and Development Program of China(No.2017YFC1700200,2017YFC1702000)+3 种基金Program of Shanghai Academic/Technology Research Leader(No.18XD1403600)Shuguang Program(No.18SG40)Program for applied basic research of Qinghai Provincial Science and Technology Department(No.2017-ZJ-713)Program for Innovative Leading Talents of Qinghai Province(2018&2019)
文摘Psoraleae Fructus(the dried fruits of Psoralea corylifolia), one of the most frequently used Chinese herbs in Asian countries, has a variety of biological activities. In clinical settings, Psoraleae Fructus or Psoraleae Fructus-related herbal medicines frequently have been used in combination with a number of therapeutic drugs for the treatment of various human diseases, such as leukoderma, rheumatism and dysentery. The use of Psoraleae Fructus in combination with drugs has aroused concern of the potential risks of herb-drug interactions(HDI) or herb-endobiotic interactions(HEI). This article reviews the interactions between human drug-metabolizing enzymes and the constituents of Psoraleae Fructus;the major constituents in Psoraleae Fructus, along with their chemical structures and metabolic pathways are summarized, and the inhibitory and inductive effects of the constituents in Psoraleae Fructus on human drug-metabolizing enzymes(DMEs), including target enzyme(s), its modulatory potency, and mechanisms of action are presented. Collectively, this review summarizes current knowledge of the interactions between the Chinese herb Psoraleae Fructus and therapeutic drugs in an effort to facilitate its rational use in clinical settings, and especially to avoid the potential risks of HDI or HEI through human DMEs.
基金the National Key Research and Development Program of China(2020YFC0845400)the NSF of China(81922070)+3 种基金Shanghai Science and Technology Innovation Action Plans(20S2190150020S21900900)supported by Shanghai Science and Technology Committeethe Three-year Action Plan of Shanghai TCM Development(ZY-(2018-2020)-CCCX-5001)Program of Shanghai Academic/Technology Research Leader(18XD1403600)。
文摘Qing-Fei-Pai-Du decoction(QFPDD)is a Chinese medicine compound formula recommended for combating corona virus disease 2019(COVID-19)by National Health Commission of the People's Republic of China.The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery,viral shedding,hospital stay,and course of the disease.However,the effective constituents of QFPDD remain unclear.In this study,an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD.A total of 405 chemicals,including 40 kinds of alkaloids,162 kinds of flavonoids,44 kinds of organic acids,71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature.With the help of the standards and in vitro metabolites,195 chemical components(including 104 prototypes and 91 metabolites)were identified in mice serum after oral administration of QFPDD.In addition,165,177,112,120,44,53 constituents were identified in the lung,liver,heart,kidney,brain,and spleen of QFPDD-treated mice,respectively.These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.
基金the National Key Research and Development Program of China (Nos.2017YFC1700200,2017YFC1702000)NSF of China (Nos.81922070, 81973286, 81973393, 81773687)+4 种基金Natural Science Foundation of Liaoning Province (No.20180530025)Program of Shanghai Academic/Technology Research Leader (No. 18XD1403600)Shuguang Program (No. 18SG40) supported by Shanghai Education Development Foundation and Shanghai Municipal Education CommissionInnovative Entrepreneurship Program of High-level Talents in Dalian (No. 2017RQ121)Undergraduate Training Program for Innovation and Entrepreneurship from Shanghai University of Traditional Chinese Medicine (No. 2017101419803010904)。
文摘Pancreatic lipase(PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae(FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL(IC50 < 10 μmol·L-1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate(4-MUO) hydrolysis, with the Ki values of 1.61, 3.77 and 10.16μmol·L-1, respectively. Furthermore, docking simulations indicated that two chalcones(isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.
基金supported by the National Key Research and Development Program of China(No.2017YFC1700200)
文摘Herbal medicines play a crucial role in the healthcare system in China and other East Asian countries,and also have been used as alternative medicines in most Western countries[1-3].However,in most cases,the metabolic fates of herbal constituents and their effects on drug metabolism or endogenous metabolism in the human body have not been well-investigated[4-5].Notably,the concomitant use of herbal medicines may lead to clinically relevant herb-drug interactions or adverse reactions or even metabolic disorders,when some herbs are co-administrated with those drugs with narrow therapeutic indices(e.g.warfarin,digoxin,thyroid hormones and some anticancer agents)[6-8].
基金the Scientific Research Funds Project of Liaoning Education Department(JDL2019012)Natural Science Fund of Liaoning Province(20180550190).
文摘Cephalotaxus is the only genus of Cephalotaxaceae family,and its natural resources are declining due to habitat fragmentation,excessive exploitation and destruction.In many areas of China,folk herbal doctors traditionally use Cephalotaxus plants to treat innominate swollen poison,many of which are cancer.Not only among Han people,but also among minority ethnic groups,Cephalotaxus is used to treat various diseases,e.g.,cough,internal bleeding and cancer in Miao medicine,bruises,rheumatism and pain in Yao medicine,and ascariasis,hookworm disease,scrofula in She medicine,etc.Medicinal values of some Cephalotaxus species and compounds are acknowledged officially.However,there is a lack of comprehensive review summarizing the ethnomedicinal knowledge o f Cephalotaxus,relevant medicinal phytometabolites and their bioactivities.The research progresses in ethnopharmacology,chemodiversity,and bioactivities of Cephalotaxus medicinal plants are reviewed and commented here.Knowledge gaps are pinpointed and future research directions are suggested.Classic medicinal books,folk medicine books,herbal manuals and ethnomedicinal publications were reviewed for the genus Cephalotaxus(Sanjianshan in Chinese).The relevant data about ethnobotany,phytochemistry,and pharmacology were collected as comprehensively as possible from online databases including Scopus,NCBI PubMed,Bing Scholar,and China National Knowledge Infrastructure(CNKI).44 Cephalotaxus"',and the respective species name were used as keywords in database search.The obtained articles of the past six decades were collated and analyzed.Four Cephalotaxus species are listed in the official medicinal book in China.They are used as ethnomedicines by many ethnic groups such as Miao,Yao,Dong,She and Han.Inspirations are obtained from traditional applications,and Cephalotaxus phytometabolites are developed into anticancer reagents.Cephalotaxine-type alkaloids,homoerythrina-type alkaloids and homoharringtonine(HHT)are abundant in Cephalotaxus,e.g.,C.lanceolata,C.fortunei var.alpina,C.griffithii,and C.hainanensis,etc.New methods of alkaloid analysis and purification are continuously developed and applied.Diterpenoids,sesquiterpenoids,flavonoids,lignans,phenolics,and other components are also identified and isolated in various Cephalotaxus species.Alkaloids such as HHT,terpenoids and other compounds have anticancer activities against multiple types of human cancer.Cephalotaxus extracts and compounds showed anti-inflammatory and antioxidant activities,immunomodulatory activity,antimicrobial activity and nematotoxicity,antihyperglycemic effect,and bone effect,etc.Drug metabolism and pharmacokinetic studies o f Cephalotaxus are increasing.We should continue to collect and sort out folk medicinal knowledge of Cephalotaxus and associated organisms,so as to obtain new enlightenment to translate traditional tips into great therapeutic drugs.Transcriptomics,genomics,metabolomics and proteomics studies can contribute massive information for bioactivity and phytochemistry of Cephalotaxus medicinal plants.We should continue to strengthen the application of state-of-the-art technologies in more Cephalotaxus species and for more useful compounds and pharmacological activities.
基金supported by the Cultivation Project of Clinical Research of Shanghai Shenkang Hospital Development Center (No.SHDC12018X30)the Natural Science Foundation of Shanghai Science and Technology Commission (No.19ZR1452100 and 20ZR 1459300)the Key Program of Yueyang Hospital of Shanghai University of Traditional Chinese Medicine (No.2019YYZ01)。
文摘Huosu Yangwei(HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD,AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.
